B cell depletion after treatment with rituximab predicts relapse of IgG4-related disease.

objectivesB cell depletion therapy with rituximab is effective in most patients with IgG4-related disease (IgG4-RD) but requires repeated cycles to prevent disease flares. We here aimed to assess B cells after rituximab to predict relapse of IgG4-RD and guide retreatment.

methodsPatients with active IgG4-RD included in this retrospective study fulfilled the ACR/EULAR Classification Criteria. Total CD19+ B cells, plasmablasts, naïve and memory B cells were measured on peripheral blood by flow-cytometry at baseline and 6 months after rituximab. All patients were treated with two 1 g infusions of rituximab 15 days apart and monitored for 48 months. Disease response was assessed using the IgG4-RD Responder Index.

resultsThirty-three patients were included. Six months after rituximab, disease response was observed in all patients. Complete depletion of CD19+ B cells, plasmablasts, naïve and memory B cell depletion was achieved in 30%, 55%, 39% and 42% of cases, respectively. Twenty-three relapses (70%) were observed at a median time of 24 months after rituximab. Relapse rate was significantly higher in patients who failed to achieve complete depletion of CD19+ cells (60% vs 17%, P = 0.02), naïve B cells (54% vs 15%, P = 0.01), or memory B cells (50% vs 16%, P = 0.03) 6 months after rituximab. The median relapse free survival time was shorter in patients who failed to achieve complete depletion of CD19+ cells (19 vs 38 months, P = 0.02), naïve B cells (16 vs 38 months, P = 0.01), or memory B cells (19 vs 38 months, P = 0.03) 6 months after rituximab.

conclusionThe degree of B cell depletion 6 months after rituximab may predict disease flare and may instruct on the pacing of B cell depletion therapy in IgG4-RD.